I’ve already devoted more time to Protandim than it deserves. I’ve written about it twice on SBM: here and here . But I can’t resist covering a new Protandim study that not only serves as a bad example but that made me laugh.

Protandim is a mixture of 5 herbal supplements intended to upregulate the body’s own production of antioxidants. Its patent application claimed that it was useful to treat or prevent an astounding 126 diseases and medical conditions, from tinnitus to aging, from hemorrhoids to cancer. At the time of my last article, only one human study had been done. It found increases in blood test markers and interpreted them as a surrogate for increased antioxidant activity in the body, but did not even attempt to assess whether those increases corresponded to any measurable clinical benefit, for cancer or for anything else. I begged Protandim supporters not to ask me about it again until there were human clinical studies with meaningful outcomes.

Now there is finally a second human study, although still not one that qualifies as a clinical trial. Curiously, it is not listed on the company’s website. I wonder why? Perhaps because it showed Protandim didn’t work. Oops.

I’m fed up! In August 2009 I wrote about Protandim, pointing out that it’s not supported by good evidence. I thought I had made myself clear; but apparently I had only made myself a target. True believers have deluged the Internet with attacks on my article, calling it mere “opinion,” ignoring its main points, and denigrating me personally. I have ignored the Internet attacks, but I’m beginning to feel personally harassed: I have lost count of the e-mails I have received from Protandim enthusiasts trying to convince me that it works and that I should change my mind. I’ve spent hours trying to explain my reasoning in e-mails, and it’s becoming a repetitive chore, so I am writing this so that next time I get an e-mail inquiry I can simply forward this link.

What Is In It?

Protandim is a mixture of milk thistle, bacopa extract, ashwagandha, green tea extract, and turmeric extract (all of which, incidentally, can be purchased individually at much lower cost).

The manufacturers of Protandim claim the product can indirectly increase antioxidant activity by up-regulating endogenous antioxidant factors such as the enzymes superoxide dismutase (SOD) and catalase, as well as the tripeptide glutathione, and by activation of theNrf2 pathway.

Nrf2 is a transcription factor that upregulates the expression of various genes that may regulate oxidative stress. Drugs to target that pathway might have benefits for diseases that are caused or exacerbated by oxidative stress. Such drugs are investigational at this point, but the makers of Protandim have skipped the investigational stage and are marketing a product that they think is effective for almost every ailment known to man and that they are promoting as an anti-aging supplement.

Four years ago I received an e-mail inquiry about Protandim. I had never heard of it; but I looked it up and wrote a quick, informal, somewhat snarky answer that got posted on the Internet. It got a lot of attention. Googling for Protandim now brings up my critique right after the Protandim website itself: that can’t be good for sales. Over the years, several e-mails and blog comments have informed me that I was wrong (usually offering testimonials or calling me closed-minded), and recently I’ve been getting inquiries asking if I’ve changed my mind now that a clinical study has been published. I haven’t.

Instead of providing antioxidants directly, Protandim is supposed to stimulate the body to produce its own antioxidants. The website tells us it is “the only supplement clinically proven to reduce oxidative stress by 40%, slowing down the rate of cell aging to the level of a 20 year old.” It provides “thousands of times more antioxidant power than any food or conventional antioxidant supplement.” It signals the body’s genes to produce the enzymes SOD (superoxide dismutase) and CAT (catalase) that act as catalysts to neutralize free radicals and are not “used up” like ingested antioxidants are. It “creates a cascade of your body’s natural catalytic antioxidants that are able to destroy millions of free radicals per second.” It raises the level of glutathione by 300%. Glutathione is good, apparently.

What is Protandim? It’s a combination of Milk thistle, Bacopa extract, Ashwagandha, Green tea extract, and Turmeric extract. I looked these up in the Natural Medicines Comprehensive Database. None of them is known to have any significant clinical benefit from antioxidant effects. Some of them are listed as “not enough information” to know if they are safe. One has estrogenic properties and more than one has known side effects and potential interactions with other drugs. The only one that even sounds remotely like it might have some pertinent data behind it is green tea. Green tea contains antioxidant catechins that are “thought to possibly have a protective effect against atherosclerosis and heart disease” and contains flavonoids that “might reduce lipoprotein oxidation; however benefits have not yet been described in humans.”

A Pubmed search for “Protandim” yielded only 3 studies: One in mice, one in cell cultures and one in humans. (more…)